DESCRIPTION This application is submitted for predoctoral fellowship support to provide training in the analytical chemistry and biochemistry of drug analysis. It is proposed that three novel ionization techniques; electrospray ionization (ESI), secondary electrospray ionization (SESI), and matrix-assisted laser desorption ionization (MALDI), be employed with ion mobility spectrometry/mass spectrometry (IMS/MS) for drug detection. IMS is already accepted as a sensitive and selective drug detection system, although it has been limited to field monitoring applications. The three ionization techniques are expected to be less sensitive to biological matrix effects which will extend the range of drug applications for IMS/MS detection. The proposed project will; (1) evaluate each ionization techniques with IMS/MS for several classes of drugs (benzodiazepines, amphetamines, opiates, and cocaine), (2) develop procedures for each biological fluid (e.g. direct injection, pre-extraction step) and (3) compare the three ionization techniques for analytical figures of merit (sensitivity, detection limit, selectivity in each biological sample, and reproducibility). Biological samples to be tested include tissue, plasma/serum, hair, and urine. NIST illicit drug-containing standards in each biological sample type will be obtained and accuracy tests will be performed. Upon completion of these goals, further research will extend into detection of other drugs (antibiotics) and conformation/protein binding studies.